title: Long-term effects of ABCB1 and SXR SNPs on the systemic exposure to cyclosporine in pediatric kidney transplant patients.
abstract: OBJECTIVE
  Cyclosporine is characterized by a wide interindividual variability in its pharmacokinetics. The objective of this study was to evaluate the effects of ABCB1 and SXR SNPs on cyclosporine exposure in a group of kidney transplant patients followed up from childhood to adulthood.
  
  
  METHODS
  Recipients were genotyped for ABCB1 C1236T, G2677T/A and C3435T, and for SXR RS3842689 and A7635G. Dose-adjusted trough levels and weight-adjusted daily doses were compared among patients according to allelic status by a generalized estimation equation approach that allows longitudinal data analyses.
  
  
  RESULTS
  A genotype-dependent effect was found in all ABCB1 genotypes and in one of the SXR SNPs. This effect was particularly evident for the TT genotype of the ABCB1 G2677T/A SNP, the TT genotype of the ABCB1 C3435T SNP and for heterozygotes of the deletion of 6 bp in the promoter region of SXR.
  
  
  CONCLUSIONS
  The presence of specific ABCB1 and SXR SNPs could significantly affect cyclosporine exposure during a kidney transplant patient's development from childhood to adulthood in a time-dependent fashion.
authors.affiliation: Department of Clinical Sciences & Community Health, University of Milan, Milan, Italy. mariano.ferraresso@unimi.it.
authors.forename: Mariano
authors.initials: M
authors.lastname: Ferraresso
authors.forename: Mirco
authors.initials: M
authors.lastname: Belingheri
authors.forename: Stefano
authors.initials: S
authors.lastname: Turolo
authors.forename: Luciana
authors.initials: L
authors.lastname: Ghio
authors.forename: Amedea Silvia
authors.initials: AS
authors.lastname: Tirelli
authors.forename: Paolo
authors.initials: P
authors.lastname: Grillo
authors.forename: Marta
authors.initials: M
authors.lastname: Lepore
authors.forename: Alberto
authors.initials: A
authors.lastname: Edefonti
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D016572:Cyclosporine / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000379:methods; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D000077297:Pregnane X Receptor; D011401:Promoter Regions, Genetic / Q000235:genetics; D011987:Receptors, Steroid / Q000235:genetics*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; D016572:Cyclosporine